DNA fragmentation of lymphocytes and sperm cells induced by nickel released from orthodontic archwires: A preliminary study.

Orthodontic brackets and archwires placed intraorally are subject to corrosion, leading to the release of cytotoxic metal ions. The aim of this study was to determine whether the use of orthodontic NiTi archwires increases systemic Ni levels and cause alterations on the DNA of cells unrelated to the oral environment such as lymphocytes and sperm cells. Human urine, semen and blood samples were collected before (baseline) sham placement of orthodontic archwires and 15 and 30 days after placement. Lymphocytes and sperm cells cells were evaluated by comet assay. Ni concentration levels in urine increased significantly between baseline and 15 days (p<0.01) and 15 and 30 days of exposure (p<0.01). Progressive decrease in sperm viability and motility was observed between the sampling periods. Lymphocytes and sperm cells showed DNA fragmentation. The increase in systemic concentration of nickel induced structural damage in the DNA of lymphocytes and human sperm cells.

Efficacy and safety of sitagliptin with basal-plus insulin regimen versus insulin alone in non-critically ill hospitalized patients with type 2 diabetes: SITA-PLUS hospital trial.

AIMS: To compare the efficacy and safety of basal-plus (BP) insulin regimen with or without sitagliptin in non-critically ill patients with type 2 diabetes (T2D). METHODS: This open-label, randomized clinical trial included inpatients with a previous diagnosis of T2D and blood glucose (BG) between 180 and 400 mg/dL. Participants received basal and correctional insulin doses (BP regimen) either with or without sitagliptin. The primary outcome was the difference in the mean daily BG among the groups. RESULTS: Seventy-six patients (mean age 60 years, 64 % men) were randomized. Compared with BP insulin therapy alone, the sitagliptin-BP combination led to a lower mean daily BG (158.8 vs 175.0 mg/dL, P = 0.014), a higher percentage of readings within a BG range of 70-180 mg/dL (75.9 % vs 64.7 %, P < 0.001), and a lower number of BG readings >180 mg/dL (P < 0.001). Sitagliptin-BP resulted in fewer basal and supplementary insulin doses (P = 0.024 and P = 0.017, respectively) and lower daily insulin injections (P = 0.023) than those with insulin alone. The proportion of patients with hypoglycemia was similar in the two groups. CONCLUSIONS: For inpatients with T2D and hyperglycemia, the sitagliptin and BP regimen combination is safe and more effective than insulin therapy alone. CLINICALTRIALS: gov identifier: NCT05579119.

Phylogenetic and Molecular Analysis of the Porcine Epidemic Diarrhea Virus in Mexico during the First Reported Outbreaks (2013-2017).

The characteristics of the whole PEDV genome that has circulated in Mexico from the first outbreak to the present are unknown. We chose samples obtained from 2013 to 2017 and sequenced them, which enabled us to identify the genetic variation and phylogeny in the virus during the first four years that it circulated in Mexico. A 99% identity was found among the analyzed pandemic strains; however, the 1% difference affected the structure of the S glycoprotein, which is essential for the binding of the virus to the cellular receptor. The S protein induces the most efficacious antibodies; hence, these changes in structure could be implicated in the clinical antecedents of the outbreaks. Antigenic changes could also help PEDV avoid neutralization, even in the presence of previous immunity. The characterization of the complete genome enabled the identification of three circulating strains that have a deletion in ORF1a, which is present in attenuated Asian vaccine strains. The phylogenetic analysis of the complete genome indicates that the first PEDV outbreaks in Mexico were caused by INDEL strains and pandemic strains related to USA strains; however, the possibility of the entry of European strains exists, which may have caused the 2015 and 2016 outbreaks.

Catheter-directed therapy for acute pulmonary embolism: results of a multicenter national registry.

INTRODUCTION AND OBJECTIVES: Catheter-directed therapy (CDT) for acute pulmonary embolism (PE) is an emerging therapy that combines heterogeneous techniques. The aim of the study was to provide a nationwide contemporary snapshot of clinical practice and CDT-related outcomes. METHODS: This Investigator-initiated multicenter registry aimed to include consecutive patients with intermediate-high risk (IHR) or high-risk (HR), acute PE eligible for CDT. The primary outcome of the study was in-hospital all-cause death. RESULTS: A total of 253 patients were included, of whom 93 (36.8%) had HR-PE, and 160 (63.2%) had IHR-PE with a mean age of 62.3±15.1 years. Local thrombolysis was performed in 70.8% and aspiration thrombectomy in 51.8%, with 23.3% of patients receiving both. However, aspiration thrombectomy was favored in the HR-PE cohort (80.6% vs 35%; P<.001). Only 51 patients (20.2%) underwent CDT with specific PE devices. The success rate for CDT was 90.9% (98.1% of IHR-PE patients vs 78.5% of HR-PE patients, P<.001). In-hospital mortality was 15.5%, and was highly concentrated in the HR-PE patients (37.6%) and significantly lower in IHR-PE patients (2.5%), P<.001. Long-term (24-month) mortality was 40.2% in HR-PE patients vs 8.2% in IHR-PE patients (P<.001). CONCLUSIONS: Despite the high success rate for CDT, in-hospital mortality in HR-PE is still high (37.6%) compared with very low IHR-PE mortality (2.5%).

Suboptimal use of ovarian function suppression in very young women with early breast cancer: a real-world data study.

PURPOSE: The incidence of breast cancer in young women (BCYW) has increased in recent decades. Malignant disease in this subset is characterized by its aggressiveness and poor prognosis. Ovarian function suppression (OFS) in these patients improves survival especially in hormone receptor-positive (HR +) cases. The Regan Composite Risk (RCR) is a prognostic tool to identify high-risk HR + BC candidates for OFS. Our study sought to characterize a Chilean cohort of early HR + BCYW assessing the use of OFS and its related prognosis and the utility of RCR in our patients. METHODS: This was a retrospective population cohort study that included ≤ 35-year-old early HR + /human epidermal growth factor receptor 2 -negative (HER2-) BC patients treated between 2001 and 2021. Analysis included clinical-pathological characteristics, treatment strategies, and survival. Also, we evaluated the association between RCR and survival. RESULTS: A total of 143 patients were included into our study, representing 2.9% of all early BC cases in our registry. Median age was 31 years old (range: 19-35). Most patients (93%) received endocrine therapy (ET). Of these, 18% received OFS. No survival differences were observed among treatment strategies. Median RCR score for patients treated with CT plus ET was significantly higher vs. ET alone (2.95 vs. 1.91; p = 0.0001). Conversely, patients treated with tamoxifen alone had significantly lower RCR scores vs. OFS (2.72 vs. 3.14; p = 0.04). Higher RCR scores were associated with poorer overall survival. CONCLUSION: Less than 20% of very young women with early HR + /HER2-BC in our cohort received OFS, in most cases, this involved surgical oophorectomy. RCR score was higher in patients that underwent CT and OFS and was associated with survival, regardless of treatment. We confirm the RCR score as a valuable prognostic tool to identify high-risk BC patients who could benefit from OFS.

Use of tramadol as analgesic alternative in Harris hawk (Parabuteo unicinctus).

BACKGROUND: The Harris hawk is a bird of prey susceptible to traumatic injuries because it is useful for several purposes such as conservancy, biological control and falconry. Once received in rehabilitation centres or specialized clinics, it is necessary to provide proper analgesia. OBJECTIVES: The aim of this study is to demonstrate the analgesic efficacy of tramadol in Harris hawks (PISADOL 50 PiSA Agropecuaria, S.A. de C.V. Calle 1 Norte, Manzana 2-25 Parque Industrial Tula Atitalaquia, Hgo, México), by the assessment of nociceptive threshold. METHODS: A total of 24 adult Harris hawks were selected from a rehabilitation centre. The birds were randomly divided into four groups: control (saline solution), 5.0, 15.0 and 30.0 mg/kg of intramuscular tramadol. Nociception was produced with electrical stimuli of 9 V, applied in propatagial skin at 1, 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300 and 360 min, assessing the nociceptive threshold and sedative effects produced by each treatment. RESULTS: No difference was observed between control and tramadol group 5 mg/kg. At 15 mg/kg, the pain threshold increased from 20 to 240 min, with minimal sedative effects. At 30 mg/kg, there was a marked increase in pain threshold from 10 to 300 min, and sedative effects like wing and head drooping for a period of 90 min. CONCLUSIONS: Tramadol can be an analgesic alternative for Harris's hawks, as it decreases the response to painful stimuli in this species when administered by intramuscular route.

Altered insulin secretion dynamics relate to oxidative stress and inflammasome activation in children with obesity and insulin resistance.

BACKGROUND: Insulin resistance (IR) is considered the main driver of obesity related metabolic complications, and is related to oxidative stress and inflammation, which in turn promote each other. There is currently no specific definition of IR in children, rather, that for adult population is used by pediatric endocrinologists instead. Altered insulin secretion dynamics are associated with worse metabolic profiles and type 2 diabetes mellitus development, thus we aimed to test whether insulin response relates to oxidative stress and inflammation in children. METHODS: We conducted a case-control study, including 132 children classified as follows: 33 children without obesity (Lean); 42 with obesity but no IR according to the American Diabetes Association criteria for adults (OBIR-); 25 with obesity and IR and an early insulin response to an oral glucose tolerance test (OGTT) (EP-OBIR +); 32 with obesity, IR, and a late insulin peak (LP-OBIR +); and studied variables associated with lipid and carbohydrate metabolism, oxidative stress, inflammation and inflammasome activation. RESULTS: The measured parameters of children with obesity, IR, and an early insulin response were similar to those of children with obesity but without IR. It was late responders who presented an impaired antioxidant system and elevated oxidative damage in erythrocytes and plasma, and inflammasome activation at their white blood cells, despite lower classical inflammation markers. Increased uric acid levels seems to be one of the underlying mechanisms for inflammasome activation. CONCLUSIONS: It is insulin response to an OGTT that identifies children with obesity suffering oxidative stress and inflammasome activation more specifically. Uric acid could be mediating this pathological inflammatory response by activating NLRP3 in peripheral blood mononuclear cells.

Predicting geographic distribution and habitat suitability of Opuntia streptacantha in paleoclimatic, current, and future scenarios in Mexico.

Mexican territory is one of the centers of origin and dispersion of the genus Opuntia, where several of its species have been an important plant resource for people in arid and semiarid zones. Opuntia streptacantha is widely distributed in Mexico; however, precise aspects of its geographic distribution and ecological status are still unknown. Here, we modeled its potential distribution under paleoclimatic, current, and future conditions through maximum entropy and predictions from 824 records and seven environmental variables. Potential distribution of O. streptacantha in the interglacial period was contracted and slightly north than current distribution, with 44,773 km2 of optimal habitat. In other past periods, the central location of potential distribution coincides with the actual current distribution, but the period of the last glacial maximum was characterized by 201 km2 of very suitable habitat, absent in interglacial, current, and future periods. The future model suggests that potential distribution will move toward the south of the Mexican territory. Synthesis and applications. The potential distribution of O. streptacantha can be applied for the conservation and management of the species, and also in the selection of areas with crassicaule scrubs for protection, conservation, and reproduction of species resistant to the hostile conditions of arid and semiarid zones of Mexican territory, where the structure and composition of the vegetation will be affected in the next 100 years.

Acid mine drainage (AMD) treatment using galvanic electrochemical system Al-Cu.

Acid mine drainage was evaluated using a galvanic (GV) electrochemical system, Al-Cu (anode/cathode), based on a 32 factorial design. The factors analyzed were anodic area/volume ratios (A/V) of 0.037, 0.072, and 0.112 cm2/cm3, and treatment time from 0.25-8 h, and analyses were performed in duplicate with 11 degrees of freedom. The response variables were the total dissolved solids and concentrations of As, Cu, Co, Cr, Pb, Fe, Ni, and SO42-. The pH, electrical conductivity, and temperature were monitored during the process. Significant differences between treatments were determined by analysis of variance with Tukey's test (p < 0.05) using Statgraphics Centurion XVI.I software. The results showed that a greater electrode surface, A/V ratio, and treatment time improved pollutant removal. The spontaneous reactions generated by the galvanic cell, through the current that flows owing to the potential difference between the Al and Cu electrodes, allows the removal of heavy metals, arsenic, and SO42- by coagulation and precipitation mechanisms. The removal efficiencies achieved were Cu (99.1%), As (76.6%), Ni (80.2%), Pb (83.6%), Cr (100%), Fe (93.71%), and 92.9% for sulfates. The X-ray diffraction and Raman analyses of the solid fraction indicated that cuprite was formed with a purity of 96%, and the recovery of Cu by the GV system may be a viable option for mining companies.

Clinical characteristics, risk factors, and outcomes in Chilean triple negative breast cancer patients: a real-world study.

BACKGROUND: Latin American (LA) studies on triple-negative breast cancer (TNBC) and their characteristics are scarce. This forces physicians to make clinical decisions based on data obtained from studies that include non-Hispanic patients. Our study sought to obtain local epidemiological data, including risk factors and clinical outcomes from a Chilean BC registry. METHODS: This was a retrospective population-cohort study that included patients treated at a community hospital (mid-low income) or an academic private center (high income), in the 2010-2021 period. Univariate and multivariate analyses were performed to identify prognostic factors associated with survival. RESULTS: 647 out of 5,806 BC patients (11.1%) were TNBC. These patients were younger (p = 0.0001) and displayed lower rates of screening-detected cases (p = 0.0001) compared to non-TNBC counterparts. Among TNBC patients, lower income (i. e., receiving treatment at a community hospital) was associated with poorer overall survival (HR: 1.53; p = 0.0001) and poorer BC specific survival (HR: 1.29; p = 0.004). Other risk factors showed no significant differences between TNBC and non-TNBC. As expected, 5-year OS was significantly shorter on TNBC versus non-TNBC patients (p = 0.00001). In our multivariate analyses TNBC subtype (HR: 2.30), locally advanced stage (HR: 7.04 for stage III), lower income (HR: 1.64), or non-screening detected BC (HR: 1.32) were associated with poorer OS. CONCLUSION: To the best of our knowledge, this is the largest LA cohort of TNBC patients. Interestingly, the proportion of TNBC among Chileans was smaller compared to similar studies within LA. As expected, TNBC patients had poorer survival and higher risk for early recurrence versus non-TNBC. Other relevant findings include a higher proportion of premenopausal patients among TNBC. Also, mid/low-income patients that received medical attention at a community hospital displayed lower survival versus private health center counterparts.

Focusing the GWAS Lens on days to flower using latent variable phenotypes derived from global multienvironment trials.

Adaptation constraints within crop species have resulted in limited genetic diversity in some breeding programs and areas where new crops have been introduced, for example, for lentil (Lens culinaris Medik.) in North America. An improved understanding of the underlying genetics involved in phenology-related traits is valuable knowledge to aid breeders in overcoming limitations associated with unadapted germplasm and expanding their genetic diversity by introducing new, exotic material. We used a large, 18 site-year, multienvironment dataset phenotyped for phenology-related traits across nine locations and over 3 yr along with accompanying latent variable phenotypes derived from a photothermal model and principal component analysis (PCA) of days from sowing to flower (DTF) data for a lentil diversity panel (324 accessions), which has also been genotyped with an exome capture array. Genome-wide association studies (GWAS) on DTF across multiple environments helped confirm associations with known flowering-time genes and identify new quantitative trait loci (QTL), which may contain previously unknown flowering time genes. Additionally, the use of latent variable phenotypes, which can incorporate environmental data such as temperature and photoperiod as both GWAS traits and as covariates, strengthened associations, revealed additional hidden associations, and alluded to potential roles of the associated QTL. Our approach can be replicated with other crop species, and the results from our GWAS serve as a resource for further exploration into the complex nature of phenology-related traits across the major growing environments for cultivated lentil.

Obesity is associated with early recurrence on breast cancer patients that achieved pathological complete response to neoadjuvant chemotherapy.

Pathological complete response (pCR) after neoadjuvant chemotherapy (NCT) is associated with good long-term prognosis in breast cancer (BC) patients. However, some patients still recur and eventually die from this disease. For years, clinical stage at diagnosis has been consistently linked to recurrence and survival in the pCR setting. Herein, we aimed to identify other potential predictors of recurrence and survival in patients that achieved pCR. We performed a retrospective analysis of patients diagnosed between 2011 and 2020 in our center. We calculated overall survival (OS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS), and BC-specific survival (BCSS). Among the 241 patients included into our study 36% were obese (Body Mass Index (BMI) > 29.9 kg/m2) and 47% were stage III. Multivariate analysis confirmed that obesity was a significant risk factor associated with early recurrence and poorer survival in these patients. In summary, obesity and clinical stage predict early recurrence and poorer survival in patients that achieved pCR after NCT. Pending further investigation and based on our findings we speculate that weight management could be beneficial for this subset of patients. To our knowledge, this is the first Latin American report linking obesity and recurrence within this setting.

Safety and efficacy of long-term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: A phase 3b, multicenter, single-arm study (STASEY).

Background: The bispecific monoclonal antibody emicizumab bridges activated factor IX and factor X, mimicking the cofactor function of activated factor VIII (FVIII), restoring hemostasis. Objectives: The Phase 3b STASEY study was designed to assess the safety of emicizumab prophylaxis in people with hemophilia A (HA) with FVIII inhibitors. Methods: People with HA received 3 mg/kg emicizumab once weekly (QW) for 4 weeks followed by 1.5 mg/kg QW for 2 years. The primary objective was the safety of emicizumab prophylaxis, including incidence and severity of adverse events (AEs) and AEs of special interest (thrombotic events [TEs] and thrombotic microangiopathies). Secondary objectives included efficacy (annualized bleed rates [ABRs]). Results: Overall, 195 participants were enrolled; 193 received emicizumab. The median (range) duration of exposure was 103.1 (1.1-108.3) weeks. Seven (3.6%) participants discontinued emicizumab. The most common AEs were arthralgia (n = 33, 17.1%) and nasopharyngitis (n = 30, 15.5%). The most common treatment-related AE was injection-site reaction (n = 19, 9.8%). Two fatalities were reported (polytrauma with fatal head injuries and abdominal compartment syndrome); both were deemed unrelated to emicizumab by study investigators. Two TEs occurred (myocardial infarction and localized clot following tooth extraction), also deemed unrelated to emicizumab. The negative binomial regression model-based ABR (95% confidence interval) for treated bleeds was 0.5 (0.27-0.89). Overall, 161 participants (82.6%) had zero treated bleeds. Conclusions: The safety profile of emicizumab prophylaxis was confirmed in a large population of people with HA with FVIII inhibitors and no new safety signals occurred. The majority of participants had zero treated bleeds.

Determining Time to Positivity of Blood Cultures in a Neonatal Unit.

Blood cultures are the gold standard for detecting bacteremia. We have studied the time to positivity of blood cultures in our neonatal unit to reduce antibiotic doses in patients with a negative blood culture. Empirical antibiotic treatment of neonatal sepsis could be withdrawn 24 hours after obtaining blood cultures.

Color doppler ultrasound for the assessment of palatal fibromucosa thickness and the trajectory of the greater palatine artery: A pilot study.

Background: The primary objective of this study was to determine the position and course of the greater palatine artery using color doppler ultrasound. The secondary objective was to determine the thickness of the palatine fibromucosa. Material and Methods: A pilot case series study was performed in a private clinic during February 2020. The scans were performed with a Mindray® M9 ultrasound machine (Mindray North America, NJ, USA) coupled to an L16-4Hs® hockey-type angled probe. For each participant, the arterial path and thickness of the palatal fibromucosa were determined at 5 different points. Results: A total of 6 volunteers (3 males and 3 females) with a mean age of 39.2 (±16) years were included. While the thickness of the fibromucosa decreased along the anterior area, the distance from the cementoenamel junction to the position of the artery was generally maintained up to the canine position, where it was found to be closed to teeth. Conclusions: Color doppler ultrasound allows accurate localization of the artery as well as measurement of the thickness of the palatine fibromucosa. It would help to select the best area for graft harvesting in order to avoid bleeding complications due to vascular sectioning. Key words:Hard palate, doppler ultrasonography, diagnosis, connective tissue graft.

Cross-Linking Pack Plus Plasma in the Mycotic Corneal Ulcer Case Report.

Fungal keratitis is a complication of refractive surgery that, if not treated in time, can lead to blindness. Given the lack of effective topical treatments for fungal ulcers, surgical treatment is necessary. The least invasive procedure is a cross-linking pack, although it has limitations when the fungus has penetrated the deep layers of the cornea. In this case report, a patient that presented a typical case of fungal corneal ulcer with hand motion perception, on the fourth day after surgery, is described. Given the nonresponse to topical antifungal treatment, plasma treatment was performed prior to cross-linking. Plasma acts by nonmechanical debridement of the ulcer, reducing the fungal colonies and allowing better penetration of riboflavin. After 6 months, the cornea remained transparent, without haze, and the patient achieved 20/25 vision.

Assessment of the Potential of a Native Non-Aflatoxigenic Aspergillus flavus Isolate to Reduce Aflatoxin Contamination in Dairy Feed.

Aspergillus species can produce aflatoxins (AFs), which can severely affect human and animal health. The objective was to evaluate the efficacy of reducing AF contamination of a non-aflatoxigenic isolate of A. flavus experimentally coinoculated with different aflatoxigenic strains in whole plant (WP), corn silage (CS), immature grains (IG) and in culture media (CM). An L-morphotype of A. flavus (CS1) was obtained from CS in a dairy farm located in the Mexican Highland Plateau; The CS1 failed to amplify the AFs biosynthetic pathway regulatory gene (aflR). Monosporic CS1 isolates were coinoculated in WP, CS, IG and CM, together with A. flavus strains with known aflatoxigenic capacity (originating from Cuautitlán and Tamaulipas, Mexico), and native isolates from concentrate feed (CF1, CF2 and CF3) and CS (CS2, CS3). AF production was evaluated by HPLC and fungal growth rate was measured on culture media. The positive control strains and those isolated from CF produced a large average amount of AFs (15,622 ± 3952 and 12,189 ± 3311 µg/kg), whereas A. flavus strains obtained from CS produced a lower AF concentration (126 ± 25.9 µg/kg). CS1 was efficient (p < 0.01) in decreasing AF concentrations when coinoculated together with CF, CS and aflatoxigenic positive control strains (71.6−88.7, 51.0−51.1 and 63.1−71.5%) on WP, CS, IG and CM substrates (73.9−78.2, 65.1−73.7, 63.8−68.4 and 57.4−67.6%). The results suggest that the non-aflatoxigenic isolate can be an effective tool to reduce AF contamination in feed and to minimize the presence of its metabolites in raw milk and dairy products intended for human nutrition.